First anti-VEGF combination therapy to show benefit in DME

Combing ranibizumab with a novel molecule targeting abnormal blood vessel growth may reduce macular edema more than treatment with ranibizumab alone, according to a phase 2a study.

Aerpio Therapeutics is investigating the ability of its first-in-class small molecule (AKB‐9778) to treat a variety of retinopathies when combined with an anti-VEGF. AKB‐9778 works by inhibiting the human protein tyrosine phosphatase β (HPTPβ) enzyme, which acts as a negative regulator of the Tie2 receptor. By inhibiting this negative regulator, Tie2 signaling is restored, overcoming the effects of the Ang2‐induced vascular destabilization.

The randomized study of 144 patients with diabetic macular edema (DME) found that combination treatment led to a clinically significant reduction in central subfield thickness compared with ranibizumab alone (P = 0.008). Additionally, there was a trend towards improved visual acuity in patients receiving combination treatment compared with ranibizumab monotherapy. No difference in adverse effects was observed.

“AKB-9778 is the first compound to show a benefit in combination with an anti-VEGF agent, the established standard-of-care, in the treatment of DME,” said Dr. David Boyer, senior partner of Retina Vitreous Associates of Los Angeles. “The robust effect seen in controlling macular edema suggests the potential of the combination of AKB-9778 and an anti-VEGF agent in the treatment of DME and other retinopathies.”